The clinical and predictive value of 18F‐FDG PET/CT metabolic patterns in a clinical Chinese cohort with autoimmune encephalitis

Abstract Aims To investigate the diagnostic and predictive role of 18F‐FDG PET/CT in patients with autoimmune encephalitis (AE) as a whole group. Methods Thrty‐five patients (20 females and 15 males) with AE were recruited. A voxel‐to‐voxel semi‐quantitative analysis based on SPM12 was used to analyze 18F‐FDG PET/CT imaging data compared to healthy controls. Further comparison was made in different prognostic groups categorized by modified Rankin Scale (mRS). Results In total, 24 patients (68.6%) were tested positive neuronal antibodies in serum and/or CSF. Psychiatric symptoms and seizure attacks were major clinical symptoms. In the acute stage, 13 patients (37.1%) demonstrated abnormal brain MRI results, while 33 (94.3%) presented abnormal metabolism patterns. 18F‐FDG PET/CT was more sensitive than MRI (p < 0.05). Patients with AE mainly presented mixed metabolism patterns compared to the matched controls, demonstrating hypermetabolism mainly in the cerebellum, BG, MTL, brainstem, insula, middle frontal gyrus, and relatively hypometabolism in the frontal cortex, occipital cortex, temporal gyrus, right parietal gyrus, left cingulate gyrus (p < 0.05, FWE corrected). After a median follow‐up of 26 months, the multivariable analysis identified a decreased level of consciousness as an independent risk factor associated with poor outcome of AE (HR = 3.591, p = 0.016). Meanwhile, decreased metabolism of right superior frontal gyrus along with increased metabolism of the middle and upper brainstem was more evident in patients with poor outcome (p < 0.001, uncorrected). Conclusion 18F‐FDG PET/CT was more sensitive than MRI to detect neuroimaging abnormalities of AE. A mixed metabolic pattern, characterized by large areas of cortical hypometabolism with focal hypermetabolism was a general metabolic pattern. Decreased metabolism of right superior frontal gyrus with increased metabolism of the middle and upper brainstem may predict poor long‐term prognosis of AE.


| INTRODUC TI ON
Autoimmune encephalitis (AE) is a debilitating inflammatory brain disorder characterized by acute or subacute onset of neuropsychiatric symptoms. 1AE is associated with autoantibodies targeting against neuronal cell surface antigens, including synaptic receptors, neuronal cell-surface proteins, or ion channels (eg, glioma inactivated 1 protein [LGI-1], and N-methyl-D-aspartate receptor [NMDAR]), or intracellular antigens (eg, glutamic acid decarboxylase 65-kDa isoform [GAD65], Hu). 2 Accurate diagnosis of AE is challenging because of the heterogeneity in clinical symptoms, low positive rate of laboratory testing tests, and lack of specificity in neuroimaging presentations. 3 The clinical manifestations of AE are varied and non-specific, including behavior problems, psychosis, seizures, and abnormal movements, often overlapped with infectious encephalitis, metabolic disease, and psychotic disorders. 4The early diagnosis of AE promotes earlier initiation of immunotherapy, which is a benefit for good prognosis. 5,6tecting neuronal antibodies in serum or cerebrospinal fluid (CSF) is critical to get a correct diagnosis.But antibody testing is not readily available in most hospitals, usually taking several weeks. 1 Failure to detect known neural autoantibodies could not rule out the suspicion of AE, and those patients without neuronal antibodies were named antibody-negative AE. 7,8 Clinical diagnostic criteria for AE developed by Graus et al. promoted the early diagnosis of AE and avoided delays in treatment caused by waiting for antibody test results. 1 For those patients with high clinical suspicion of AE, these criteria required the combination of clinical history and auxiliary examination results, including electroencephalogram (EEG) and magnetic resonance imaging (MRI), regardless of the availability of antibody tests.In the workup of suspected AE, head MRI, as the most common imaging technique used in AE presented the limited value.The increased T2/fluid-attenuated inversion recovery (T2/FLAIR) signal may involve multiple brain regions including cerebral cortex, cerebellum, striatum, brainstem with or without enhancement.
Additionally, more than 50% of patients with AE demonstrated normal or nonspecific MRI results. 9There is an urgent need to identify a more sensitive neuroimage biomarker aiding the diagnosis of AE.
Several studies have suggested 18 F-FDG PET/CT has higher sensitivity than MRI in assisting diagnosis. 10lnes et al. found 18 F-FDG PET/CT was more often abnormal compared to patients with AE with MRI results during the diagnostic period (22/23, 95.6% vs. 10/23, 43%). 11Besides, some specific metabolic patterns associated with certain types of AE or special symptoms have been identified.For patients with anti-NMDAR encephalitis, abnormalities in 18 F-FDG PET/CT were frontotemporal hypermetabolism and occipital hypometabolism, followed by metabolic normalization with recovery. 12Basal ganglia (BG) hypermetabolism implied the potential involvement with facio-brachial dystonic seizures (FBDS). 13The decrease in the cortex/striatal metabolic ratio served as an imaging biomarker for the differentiation of patients with AE from mild cognitive impairment (MCI). 14However, the Graus criteria mentioned 18 F-FDG PET/CT as an alternative to MRI only for the definition of definite AE. 1 The role of 18 F-FDG PET/CT in subjects with possible AE or probable AE needs more evidence.
Most previous works were restricted to delineate metabolic patterns on a specific autoantibody or a single syndrome, rather than on the whole AE group. 14In addition, brain PET images for semi-quantitative analysis were extracted from whole-body 18 F-FDG PET/CT, reducing the spatial resolution of imaging data. 12 18 -FDG PET/CT studies on AE have been limited to visual interpretation or mingle with a certain proportion of patients after the acute stage of disease. 13,15In the present study, we aimed to determine the brain metabolic patterns of glucose metabolism changes in a cohort of patients suffering from AE, including both antibody-positive AE and antibody-negative AE, in comparison to healthy controls matched on sex and age, using Statistical Parametric Mapping (SPM) analysis.Furthermore, we investigated the correlation of metabolism patterns with the condition of longterm prognosis in patients with AE.

| Participants selection
A single-center retrospective study was conducted at Xiangya Hospital, Central South University from January 2016 to December 2020.The study was approved by the Medical Ethics Committee with increased metabolism of the middle and upper brainstem was more evident in patients with poor outcome (p < 0.001, uncorrected). 18F-FDG PET/CT was more sensitive than MRI to detect neuroimaging abnormalities of AE.A mixed metabolic pattern, characterized by large areas of cortical hypometabolism with focal hypermetabolism was a general metabolic pattern.

Conclusion:
Decreased metabolism of right superior frontal gyrus with increased metabolism of the middle and upper brainstem may predict poor long-term prognosis of AE.
of Xiangya Hospital, Central South University, and was carried out in compliance with the Declaration of Helsinki.Written Informed consent for inclusion in this study and publication for clinical details were obtained from each participant involved in this study.
During this period, a total of 340 adults diagnosed with suspected AE were referred to our hospital, of whom 45 patients were performed with cerebral 18 F-FDG PET imaging.After reviewing their electric medical recording carefully, 10 patients were excluded by (1)   6 patients who underwent PET scanning after the acute stage of disease; (2) 2 patients had incomplete clinical information; (3) 2 patients modified the final diagnosis with Creutzfeldt-Jakob disease.Finally, 35 patients with AE were recruited for this study (Figure 1).(2) antibody-negative AE: the diagnosis was made when all three of the following criteria have been met 16,17 : (i) none of the known neuronal antibody was identified in the serum or CSF sampling;

The inclusion criteria
(ii) ≥1 feature present: CSF-specific oligoclonal bands; intrathecal synthesis of immunoglobulin or elevated CSF IgG index; CSF pleocytosis (>5 cells/mm 3 ) or elevated protein; brain MRI abnormalities suggestive of AE; effective immunotherapy; (iii) reasonable exclusion of alternative causes.These patients were sorted into Ab-negative-LE, probable-AE, possible-AE. 18Two experienced neurologists reviewed the medical record and made the corresponding classification (Yuwei Dai and Yuanyuan Xie).
The data concerning demographic information, clinical characteristics, associated neoplasia, treatment regimes, treatment delay as expressed in weeks between the onset of symptoms, and the duration of symptom onset and 18 F-FDG PET/CT were collected by reviewing patients' charts and databases.First-line immunotherapy included intravenous methylprednisolone pulse (IVMP), intravenous immunoglobulin (IVIG), and plasma exchange (PLEX); rituximab (RTX) and cyclophosphamide served as second-line immunotherapy.The levels of consciousness of enrolled patients were evaluated based on the Glasgow Coma Scale (GCS) score on admission.GCS scores lower than 8 (GCS≤8) indicated decreased level of consciousness. 19Forty-three age-matched, gender-matched volunteers without any neurological or psychiatric illness were enrolled as healthy controls.

| Exclusion of infectious etiologies
Infectious evaluations of serum and CSF were performed for all patients as a diagnostic procedure of AE.The following measures were adopted to exclude possible infectious etiologies: Gram stain and India ink stain; aerobic and anaerobic bacterial cultures; mycobacterium culture and acid-fast bacillus stain; fungal culture; immunoglobulin M (IgM) and IgG specific for parasites; polymerase chain reaction (PCR) tests for enterovirus, Epstein Barr virus (EBV), herpes simplex virus (HSV) 1 and 2, varicella-zoster virus, or human herpes F I G U R E 1 Flowchart of enrolled patients with autoimmune encephalitis.virus 6.No definite evidence of infection was found in these enrolled cases.

| Neuronal antibody detection
For every patient with suspected AE, comprehensive neural antibody studies were conducted in serum and CSF, including both indirect immunofluorescence assay (IIFA) fixed by rat brain tissues for unknown antibodies and commercial workup panels for known antibodies.

| Evaluation and follow-up of long-term prognosis
Two neurologists (Xianghe Liu and Lili Long) retrospectively evaluated the severity of clinical symptoms by a comprehensive scale proposed recently, the Clinical Assessment Scale in Autoimmune Encephalitis (CASE). 21Meanwhile, the modified Rankin Scale (mRS) was also conducted to evaluate the neurological disability of all patients. 22The CASE score (range: 0-27) and mRS score (range: 0-6) were obtained at four time points (at admission, at disease peak, at discharge, and at the last follow-up) based on medical records.
Responders to treatment were defined as the decrease of at least 1 point in mRS score after immunotherapy. 18e follow-up was achieved via subsequent outpatient visits.
The long-term outcomes were evaluated at least 1 year from disease onset. 6Patients were categorized into two groups based on the mRS score at the last follow-up: good outcome (mRS: 0-2) and poor outcome (mRS: 3-6).

| Review of brain MRI
Patients' brain MRIs were collected using 3.0-Tesla or 1.5-Teala MAGNETOM Verio scanner (Siemens, Germany) in Xiangya Hospital, Central South University.The following sequences were acquired: T1-weighted images (T1WI), T2-weighted images (T2WI), fluid-attenuated inversion recovery (FLAIR), diffusion-weighted images (DWI), and gadolinium-enhanced images.In the case of multiple MRI examinations, MRI data interpretation primarily focused on the results nearest to the onset of symptoms.MRI images with evidence of underlying encephalitis or inflammatory changes (T2 or T2/FLAIR hyperintensities restricted to one or both mesial temporal lobes, or multifocal in gray matter, white matter, or both in the cerebral cortex, cerebellum, striatum, brainstem) were considered as positive.
Blinded interpretation of MRI results was conducted by two experienced radiologists.

| 18 F-FDG PET/CT scanning
All subjects accepted 18 F-FDG PET/CT scanning at the PET Center of Xiangya Hospital, Central South University using a Discovery Elite PET/CT scanner (GE Healthcare, Boston, MA, United States) during the acute phase of the disease.All participants were required to fast for at least 6 h and discontinue all steroid hormones or antiseizure drugs (ASDs) for at least 24 h.Fasting blood glucose levels of all patients did not exceed 8 mmol/L before injection of 18 F-FDG. 18F-FDG was intravenously injected following a dose of Once the PET images were preprocessed, a two-sample t-test was conducted to delineate metabolic pattern characteristics of single subjects with age and gender as the nuisance variables, comparing each patient with the control group.FDG uptake was compared voxel-to-voxel between patients and the control group using two-t-sample-test of SPM.We also compared AE patients with good outcomes between AE patients with poor outcome using the same way to the predictive value of 18 F-FDG-PET biomarkers on longterm prognosis.Metabolic changes were considered statistically significant at the strict threshold (p < 0.001) and corrected for multiple comparisons (family-wise error [FWE] corrected, p < 0.05) with cluster size (K E ) above 20 contiguous voxels.If significant metabolic changes were not found, a more lenient threshold was set (p < 0.001, uncorrected; K E = 20 voxels).

| Statistical analysis
Continuous variables were described using means ± standard deviation (SD) or median (interquartile range [IQR]).The counting data were presented as percentages (%).Continuous variables were tested to determine whether they conformed to a normal distribution by the Shapiro-Wilk normality test first.For the univariate analysis of poor long-term outcomes, continuous variables were compared using the t-test or non-parametric Mann-Whitney Utest, and Fisher's exact tests were used for categorical variables.
The variables with p values < 0.05 on univariate analysis were further selected by the least absolute shrinkage and selection operator (LASSO) regression using the R software package glmnet. 23  disease peak, at discharge, at the last follow-up were 5.0, 5.0, 3.0, and 2.0.The median CASE scores at admission, at disease peak, at discharge, at the last follow-up were 5.0, 7.0, 4.0, and 3.0.

| PET imaging analysis
The details of imaging results (both MRI and 18 F-FDG PET/CT) for individual patients were summarized in Table S2

| Univariate analysis of predictors of poor long-term outcome
In this study, after the median follow-up time of 26.0 months (IQR: 20.0-40.0)since disease onset, the median score on the mRS scale was 2 points (IQR:1-4).A good outcome was achieved in 18 patients (18/35, 51.4%), while 17 showed a poor long-term outcome (17/35, 48.6%), in which 4 patients died (4/35, 11.4%).The median interval between the last follow-up and disease onset of patients with good outcome was 30.5 months (IQR:13.5-46.5),while 25.0 months (IQR: 20.5-39.5) in the group with bad outcome.We found no significant statistical difference between the two subgroups (p = 0.590) during the follow-up interval of this study.

The comparison of demographic and clinical information among
two subgroups is shown in Table 2.The mean age of patients with poor long-term outcome was 50.76 ± 18.4 years, whilst the mean age of the good long-term outcome group was 37.39 ± 15.9 years (p = 0.028).The rate of decreased level of consciousness in the good and poor outcome groups was 1/18 (5.6%) and 7/17 (41.2%), respectively (p = 0.018).Besides, 29.4% (5/17) experienced central hypoventilation in poor outcome group, which was significantly higher than that in the good outcome group (0/18, p = 0.019).Patients with poor outcomes also had a higher tumor incidence than the good outcome group (p = 0.019).The poor outcome group tended to have a lower percentage of receiving second-line immunotherapy, compared with good outcome group (p = 0.027).There was no statistical significance in gender composition, some primary clinical symptoms (seizure, psychiatric symptoms, ataxia), and the rate of intensive care unit (ICU) admission (all p > 0.05).On antibody examination, antibody positive detection rate, or antibodies against intracellular antigens positive detection rate did not show any statistical differences among the two subgroups (both p > 0.05).Both groups did not differ in their mRS scores and CASE scores at disease peak (both p > 0.05).No difference was found in the interval from symptoms onset to initiation of immunotherapy (p = 0.351) or the proportion of first-line immunotherapy (p = 1.000).There was no statistically significant difference in the time interval between the two groups receiving PET examinations (p = 0.424).The proportion of steroids or sedatives usage before PET scanning in the two subgroups also had no statistical difference (both p > 0.05).The rate of relapse or median time to relapse was similar in patients with good outcome and patients with poor outcome (both p > 0.05).Older age, reduced consciousness, central hypoventilation, tumors, and less usage of second-line immunotherapy were more likely to be at risk of poor prognosis.

| Prognostic value of PET imaging
Further semi-quantitative group analysis of metabolic patterns based on SPM found that patients with AE with poor outcomes showed decreased metabolism of the right superior frontal gyrus along with increased metabolism of the middle and upper brainstem, mainly located in bilateral pons, compared with those with good outcomes (p < 0.001, uncorrected, Figure 4).

| DISCUSS ION
In this present study, we retrospectively investigated cerebral metabolic patterns of 35 patients with AE in the acute stage based on a voxel-based analysis of SPM, then we searched candidate neuroimage prognostic biomarkers of AE.Rather than limiting our focus to a specific antibody-mediated encephalitis, we TA B L E 2 Comparison of basic information between patients with AE with good long-term outcome and poor long-term outcome.For AE, as a group of complicated and treatable neuroinflammation conditions mediated by autoimmune antibodies, early diagnosis is essential to prompt initiation of immunotherapy thus generating a positive outcome. 24Although a clinical approach to diagnosis AE has emerged recently, 1 many patients with suspected AE might be misdiagnosed first as "psychiatric patients" and miss the optimal timing for intervention, mostly due to the presence of antibodynegative patients with AE or delay of antibody testing. 25,26Besides, most patients with AE were clinically characterized by various and unspecific symptoms with normal or non-specific findings of serum or CSF sampling, EEG and MRI, both in previous reports and our reports. 14As a major diagnostic imaging tool, the diagnostic value of MRI was limited.In our report, the proportion of MRI negative was as high as 62.9% as in previous reports. 4Probasco et al. also found that only 40% of patients with AE had consistent abnormal MRI findings. 27merous studies began to focus on the diagnostic value of 18 F-FDG PET/CT on AE. 11 It has been widely reported that PET was more sensitive to detecting abnormal findings in AE than MRI. 28A recent systematic review encompassed 21 publications and 444 patients with AE, from which 87% (80-92%) showed alterations in brain FDG-PET images.The high detection sensitivity of 18 F-FDG PET/CT was in concordance with our results (94.3%). 10For 13 patients with abnormal MRI, lesions confirmed by MRI roughly corresponded to lesions with glucose metabolic abnormalities from PET images, indicating a better consistency between MRI and 18 F-FDG PET/CT.94.3% of patients presented a mixed metabolic pattern, characterized by large areas of cortical hypometabolism with focal hypermetabolism.The discrepancy between MRI and 18 F-FDG PET/ CT in detection rates of AE might be explained by neuronal dysfunction in the absence of structural alteration. 29e usefulness of brain 18 F-FDG PET/CT imaging has been acknowledged by the latest diagnostic criteria of LE.The guideline stated bilateral FLAIR/T2 abnormalities of MTL were required, and 18 F-FDG PET/CT hypermetabolism in bilateral MTL could serve as an alternative in the absence of such findings. 27A prospective study enrolled 104 pediatric patients with suspected AE and concluded brain 18 F-FDG PET/CT had higher specificity, sensitivity, and accuracy for diagnosis of AE in clinically suspected AE children.Nearly 60% of children with AE showed extensive hypometabolism in more than one lobe or one lobe with focal hypermetabolism, which supported evidence for the diagnosis in children with suspected AE. 16 Mixed metabolic patterns may become common features of AE in both adults and children.
Moreover, a systematic review tried to clarify distinct metabolic patterns of 18 F-FDG PET/CT among different AE subtypes, mainly focusing on anti-NMDAR encephalitis and anti-LGI1 encephalitis. 30 anti-NMDAR encephalitis, PET findings revealed hypermetabolism in temporal lobe with/without metabolic alteration in cortical regions. 3,30Mixed patterns of hyper-and hypo-metabolism, characterized by frontal lobe hypometabolism combined with temporal lobe and right cerebellum hypermetabolism were detected in patients with anti-NMDAR encephalitis of our cohort.The brain metabolism patterns of anti-NMDAR encephalitis based on SPM in our cohort were shown in Figure S1.However, regarding the expensive cost and radioactivity of 18 F-FDG PET/CT, we proposed that brain 18 F-FDG PET/CT could be considered as a diagnostic tool under the following conditions: highly suspected AE but no positive paraclinical findings or paraneoplastic syndromes suggesting for the presence of tumors.
The proportion of good prognosis in our present study was 51.4%.
Similarly, a recent multi-center study conducted in Eastern China revealed that good clinical outcomes were achieved in 117 (63.24%)AE patients with a follow-up period of at least 1 year. 31In our report, we have identified five variables associated with the long-term outcome of AE using a univariate analysis: age, presence of potential neoplasm, level of consciousness, central hypoventilation, and the use of second-line immunotherapy.However, further multivariate analysis showed that only a decreased level of consciousness was identified as an independent predictive risk factor.Chi et al. also found that a GCS score ≤8 at admission was significantly associated with an increased risk of mortality in patients with anti-NMDAR encephalitis. 19Those with reduced level of consciousness were more likely to have a combination of severe complications, such as pneumonia and some infections, which might prolong recovery time. 32There is still no unified conclusion on the clinical variables affecting AE prognosis, heterogeneous study design, or different criteria for judging ending points produced conflicting results. 13In our study, patients with good outcome tended to have shorter interval between disease onset and immunotherapy initiation and to receive more second-line immunotherapy, even if these variables did not reach statistical significance.This indicated that neurologists should initiate immunotherapy in patients with suspected AE as soon as possible.
Previous studies have tried to find representative neuroimage biomarkers serving as prognostic factors of AE, mostly focusing on MRI findings.In a case series of 41 patients with AE, Byun et al.
found that normal MRI presentation was associated with seizure remission in half a year. 33It was also reported that diffuse cerebellar atrophy revealed by MRI often indicated a poor prognosis of anti-NMDAR encephalitis. 34To our knowledge, less research has focused on the application of 18 F-FDG PET as a predictive biomarker to predict the long-term outcome of AE.Among patients with anti-NMDAR encephalitis, marked medial and lateral occipital lobe hypometabolism was more evident in those with were as follows: (1) subacute onset of neurological symptoms (working memory deficits, seizure, decreased level of conscience, movement disorders, unexplained dysautonomia, or abnormal movements) or psychiatric symptoms (behavior changes, disturbances in mood or character, hallucinations, speech dysfunction); (2) at least one of the following abnormalities: CSF with pleocytosis (white blood cell count of more than 5 cells per mm 3 ), CSF oligoclonal bands or elevated IgG index, CSF elevated protein, abnormal EEG, MRI features suggestive of AE; (3) taking the PET examination in a relatively acute disease course, according to previous definition of the acute phase (within 3 months) and chronic phase (over 3 months) of AE 1,13 ; (4) reasonable exclusion of alternative causes.All patients were further classified as (1) antibody-positive AE based on Graus criteria 1 : autoimmune neuronal antibodies were detected in CSF and/or serum, including definite-AE, antibody-positive limbic encephalitis (Ab-positive-LE), and anti-NMDAR encephalitis;

3. 7
MBq/kg within 1 min.Before PET scan acquisition, participants were allowed to rest quietly in a dedicated room for an hour.A low-dose CT scan (120 kV, 60-180 mA/s, slice thickness 3.75 mm) was started first, brain PET scanning was performed for 15-20 min followed by whole-body PET scanning for 35-45 min.The wholebody PET scans ranged from the top of the head down to midthigh, to screen occult tumors.The full width of the scan at half maximum was 5.4 mm.The brain images were reconstructed into a 192 × 192 trans-axial matrix (35 cm field of view) using the 3D VUE Point (GE Healthcare) ordered-subset expectation-maximization algorithm.CT images were obtained for attenuation correction simultaneously.2.7 | 18 F-FDG PET/CT imaging analysis PET imaging data were analyzed by SPM12 software (Welcome Department of Cognitive Neurology, London, United Kingdom), implanted in MATLAB 2018a (MathWorks Inc., Sherborn, MA, USA) environment.The image preprocessing steps were as follows: scans from all individuals were firstly segmented and spatially normalized into standard stereotactic Montreal Neurological Institute (MNI) space with voxel sizes of 2 mm × 2 mm × 2 mm.Then, normalized images were smoothed by an 8-mm Full-Width Half-Maximal (FWHM) 3D Gaussian kernel to increase the signalto-noise ratio.Subsequently, PET image values were processed to intensity normalization, performed by proportional scaling to overall activity.
The features selected by LASSO regression were subsequently entered into the multivariate Cox proportional hazards regression model.The strength of association was evaluated by Hazard ratios (HR) and corresponding 95% confidence interval (CI) in the multivariate Cox regression model.A two-tailed p-value < 0.05 was considered significant.Statistical analyses were performed with SPSS 26.0 software package for Windows (IBM Corp.) and R language (version 4.3.3).

Five
features identified by univariate analysis were further selected by LASOO regression.Three variables (decreased level of consciousness, tumors, combined with second-line immunotherapy) selected by LASSO regression were finally included in a multivariate Cox regression model.These results were presented in F I G U R E 2 Corresponding MRI images, abnormal cerebral glucose metabolism patterns and 18 F-FDG PET/CT results based on SPM of 4 patients with AE. (A) MRI imaging, (B) cerebral glucose metabolism patterns, (C) 18 F-FDG PET/CT results based on SPM (p < 0.05, FWE corrected).The hypermetabolism regions were shown in orange-red color, and hypometabolism regions were shown in blue-green color. 18F-FDG PET/CT, 2-deoxy-2-18 Ffluoro-D-glucose-( 18 F-FDG) positron emission tomography/computed tomography; AE, autoimmune encephalitis; FWE, family-wise error; MRI, magnetic resonance imaging; SPM, Statistical Parametric Mapping.Table 3.The multivariate analysis results showed that decreased level of consciousness was independently associated with poor outcome of AE (HR = 3.591, 95% CI = 1.272-10.375;p = 0.016).No significant association was found in other predictors of poor prognosis, including tumors or combined with second-line immunotherapy (p > 0.05).

F I G U R E 4 | 11 of 13 DAI
Metabolic results of two-sample t test group analysis between two different prognostic subgroups (p < 0.001, uncorrected).Slice view (A) and render view (B) were created by xjView toolbox (https:// www.alive learn.net/ xjview/ ).The hypermetabolism regions were shown in orange-red color, and hypometabolism regions were shown in blue-green color.et al.focused the identification of AE as a whole, not only those with antibody-positive AE but also those with antibody-negative AE.There were three significant implications of our study, first, in comparison with MRI,18 F-FDG PET/CT might be more often abnormal sensitive in the acute stage of AE; then, a mixed metabolic pattern, characterized by large areas of cortical hypometabolism with focal hypermetabolism, was a typical finding of AE in acute stage.Lastly, decreased metabolism of right superior frontal gyrus along with increased metabolism of the middle and upper brainstem might be associated with a poor prognosis for patients with AE.These results provided clues for the application of18 F-FDG PET/CT in the diagnosis and clinical management of AE.
White blood cell (WBC) counts in the CSF of 12 subjects were mildly increased (12/35, 34.3%).9 (9/35, 25.7%) had elevated cerebrospinal fluid protein levels CSF protein.Among 25 patients who were tested for CSF oligoclonal bands, 60% (15/25, 60.0%) reported a positive result.Twenty patients completed 24-h dynamic or video Not available CASE score for four dead patients at the last follow-up.

Variables Good long-term outcome (mRS: 0-2), n = 18 Poor long-term outcome (mRS: 3-6), n = 17 p value
Test or Mann-Whitney U-test was used for continuous variables.Multivariate analysis of risk factors associated with poor long-term outcome in patients with autoimmune encephalitis.
a t-